Advances in clinical and experimental medicine : official organ Wroclaw Medical University · 2015
Cytotoxic activity of valproic acid on primary chronic lymphocytic leukemia cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Karp Marta, Kosior Kamila, Karczmarczyk Agnieszka, Zając Małgorzata, Zaleska Joanna, Tomczak Waldemar, Chocholska Sylwia, Hus Marek, Dmoszyńska Anna, Giannopoulos Krzysztof
Аннотация
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in western civilization. The accumulation of CD5+CD19+ B lymphocytes in peripheral blood is due to a defect in the apoptotic pathway rather than excessive proliferation in the bone marrow and lymph nodes. Despite a number of treatments, CLL remains an incurable disease. Valproic acid (VPA) activity, as a histone deacetylase inhibitor, could restore the epigenetic changes underlying the pathogenesis of CLL and thus induce cell death.
OBJECTIVES: In the present study we hypothesized that VPA could induce CLL primary cells death through activation of apoptosis.
MATERIAL AND METHODS: Peripheral blood samples were obtained from 53 CLL patients. Peripheral blood mononuclear cells were isolated through density gradient centrifugation and were the subject of a 24-hour cell culture with 10 mM of VPA. The cytotoxic effect of VPA was evaluated with an XTT test and thereafter confirmed using Annexin V-FITC/PI staining and flow cytometry techniques.
RESULTS: In this study, a median VPA cytotoxicity of 13.88% with a range of 0-54.65% was observed. Annexin V/PI staining confirmed that the demonstrated cytotoxicity was caused by increased apoptosis in the VPA treated cells as compared to control cells. Statistical analysis showed that VPA's effect on CLL cells depends on lactate dehydrogenase serum levels, but is independent of all other prognostic markers.
CONCLUSIONS: The results of the present experiments found that VPA at a clinically applicable concentration significantly induces apoptosis independently of the disease stage and might be a valuable therapeutic agent for all CLL patients.
OBJECTIVES: In the present study we hypothesized that VPA could induce CLL primary cells death through activation of apoptosis.
MATERIAL AND METHODS: Peripheral blood samples were obtained from 53 CLL patients. Peripheral blood mononuclear cells were isolated through density gradient centrifugation and were the subject of a 24-hour cell culture with 10 mM of VPA. The cytotoxic effect of VPA was evaluated with an XTT test and thereafter confirmed using Annexin V-FITC/PI staining and flow cytometry techniques.
RESULTS: In this study, a median VPA cytotoxicity of 13.88% with a range of 0-54.65% was observed. Annexin V/PI staining confirmed that the demonstrated cytotoxicity was caused by increased apoptosis in the VPA treated cells as compared to control cells. Statistical analysis showed that VPA's effect on CLL cells depends on lactate dehydrogenase serum levels, but is independent of all other prognostic markers.
CONCLUSIONS: The results of the present experiments found that VPA at a clinically applicable concentration significantly induces apoptosis independently of the disease stage and might be a valuable therapeutic agent for all CLL patients.